1. Field of the Invention
This invention relates to a sustained release drug delivery device and, in particular, to a device for the transdermal or percutaneous delivery of drugs. The invention relates especially to a device for the systemic delivery of drugs by the transdermal route.
The advantages of administering certain drugs by the transdermal route are well known and include avoidance of drug deactivation by digestive enzymes or first-pass hepatic metabolism. However, these advantages are also characteristic of drug administration by parenteral routes such as by intramuscular injection or i.v. infusions.
2. Description of the Prior Art
Transdermal delivery for systemic therapy has been recognized as feasible for some considerable period of time, on the basis of ointment preparations of nitroglycerin, anti-inflammatory agents and hormones. For example, topical nitroglycerin ointment has been used in the United States of America for angina prophylaxis since the 1950s.
Until relatively recently--circa 1980--only parenteral administration offered precise control over rate of drug entry into the bloodstream and then only when closely monitored.
A number of transdermal devices have now been developed and consist essentially of transdermal or skin patches. Certain of these transdermal devices include a rate-controlling membrane between a drug reservoir and the skin surface. The rate-controlling membrane limits the amount of drug delivered per unit area of skin surface in a manner such that the device and not the skin is dominant in controlling the rate of drug input to the skin surface and hence to the systemic circulation.
A number of transdermal nitroglycerin patches are now on the U.S. market and are indicated for the prevention and treatment of angina pectoris due to coronary artery diseases. Although there are differences in composition, mechanism of drug delivery and appearance among the currently available transdermal nitroglycerin device all appear to be functionally similar. Examples of transdermal nitroglycerin patches are those marketed by Ciba Pharmaceutical Company under the trademark TRANSDERM-NITRO and manufactured by Key Pharmaceuticals, Inc under the trademark Nitro-Dur.
It is expected that these transdermal devices will largely replace nitroglycerin ointment in prophylactic angina therapy, since the ointment can be messy and needs to be applied several times a day because it retains its effectiveness for only 4-8 hours. Accordingly, patient acceptance and compliance can be a problem with such therapy.
It will be appreciated, however, that with transdermal therapy it is ultimately the inherent permeability of the skin that determines skin absorption of a drug and hence its delivery into the systemic circulation.
It has been established that the molecular permeability of skin is a passive rather than a biologically active property and that the stratum corneum, in particular the interstitial lipid phase thereof, is the principal barrier to drug permeation. It has been shown by Elias, P. M. et al (c.f., Clinical Research Vol. 30 No. 1, 1982) that regional differences in skin permeability may be related to regional differences in specific lipid content of the epidermis.
All of the currently available transdermal or skin patches discussed above are secured to the skin by a layer of adhesive extending over the skin-contacting surface of the device. In the case of the above-mentioned nitroglycerin patches it is recommended that the patches be applied to a hairless region of the body such as the upper arm or chest. Shaving of a suitable area for application of the patch may be necessary. However, shaving may cause local skin irritation and change the permeability characteristics of the products. All the currently available transdermal products are approved for once-daily administration and it is recommended that one alternates application sites daily.
It will be appreciated that the repeated application and removal of such patches, involving a securing layer of adhesive, can result in skin irritation and sensitization with prolonged use. It will also be appreciated that a certain amount of pain and discomfort is experienced on removing the patches.
It will also be appreciated that the currently available transdermal devices are of a relatively complicated design, including as they do various rate-controlling delivery systems, and consequently are relatively costly.
Conventionally, nitroglycerin ointment or cream has been applied to a given area of the body such as the chest by squeezing a predetermined amount of ointment onto a piece of paper and applying the paper with the ointment loaded thereon to the body, the ointment providing the necessary adhesion of the paper to the body.
Generally, the paper applicator used consists of a ruled piece of waxed paper. When one wishes to apply a given quantity of active ingredient carried by the ointment one squeezes a given amount of the ointment, for example one inch, from a tube onto the ruled piece of waxed paper in accordance with the drug manufactures' package directions.
The paper in addition to serving as an applicator for the ointment, provides a protective layer over the ointment and prevents the ointment from coming into contact with the hands of a nurse or other person applying the ointment to the skin.
However, the paper does not ensure a unidirectional transfer of the nitroglycerin or other active ingredient to the skin. Nitroglycerin for example will migrate through the paper and escape into the atmosphere. Effectively, the nitroglycerin can leave the site of application in any direction and, accordingly, the potential effect of topical nitroglycerin therapy is correspondingly reduced.
It is an object of the present invention to provide a transdermal device which incorporates a drug suitable for transdermal administration in an ointment carrier and which ensures a unidirectional transfer of the drug to the skin.